Our overall goal is to understand the molecular details of estrogenic hormone action in uterine tissue. A theme common to all the proposed studies is regulation of nuclear function. Three areas of target cell function will be examined. First, we propose to examine DNA synthesis which is stimulated 18 to 24 hours after hormone administration. We are particularly interested in the role of initiator RNA and whether the estrogen-receptor complex may have a role in its synthesis. We are also interested in the refractory state of DNA synthesis which is brought about by 3 days of estrogen injections. The second area we will explore concerns the so-called "estrogen-induced protein" (IP) of the uterus. We will attempt to assay for IP mRNA as well as determine whether other specific RNAs are made in response to estrogen. Because the IP-RNA synthesis appears to be one of the earliest responses to estrogen and because it is one of the few in vitro responses, it is assumed to be closely related to the initial action of the estrogen receptor. A third area of investigation will be to develop cell cultures of uterine tissue in which estrogen binding, nuclear translocation and estrogen response studies can be carried out.